METK2_MOUSE
ID METK2_MOUSE Reviewed; 395 AA.
AC Q3THS6; Q3TL60; Q76LX3;
DT 24-JAN-2006, integrated into UniProtKB/Swiss-Prot.
DT 24-JAN-2006, sequence version 2.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=S-adenosylmethionine synthase isoform type-2;
DE Short=AdoMet synthase 2;
DE EC=2.5.1.6 {ECO:0000250|UniProtKB:P31153};
DE AltName: Full=Methionine adenosyltransferase 2;
DE Short=MAT 2;
GN Name=Mat2a;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=ddY; TISSUE=Kidney;
RA Sakata S., Okumura S.;
RT "cDNA for mouse kidney methionine adenosyltransferase II alpha.";
RL Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and DBA/2J;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [4]
RP POST-TRANSCRIPTIONAL REGULATION.
RX PubMed=29262316; DOI=10.1016/j.celrep.2017.11.092;
RA Shima H., Matsumoto M., Ishigami Y., Ebina M., Muto A., Sato Y.,
RA Kumagai S., Ochiai K., Suzuki T., Igarashi K.;
RT "S-Adenosylmethionine synthesis is regulated by selective N6-adenosine
RT methylation and mRNA degradation involving METTL16 and YTHDC1.";
RL Cell Rep. 21:3354-3363(2017).
CC -!- FUNCTION: Catalyzes the formation of S-adenosylmethionine from
CC methionine and ATP. The reaction comprises two steps that are both
CC catalyzed by the same enzyme: formation of S-adenosylmethionine
CC (AdoMet) and triphosphate, and subsequent hydrolysis of the
CC triphosphate. {ECO:0000250|UniProtKB:P31153}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + L-methionine = diphosphate + phosphate + S-
CC adenosyl-L-methionine; Xref=Rhea:RHEA:21080, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:57844, ChEBI:CHEBI:59789; EC=2.5.1.6;
CC Evidence={ECO:0000250|UniProtKB:P31153};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P0A817};
CC Note=Binds 2 magnesium ions per subunit. The magnesium ions interact
CC primarily with the substrate. {ECO:0000250|UniProtKB:P31153};
CC -!- COFACTOR:
CC Name=K(+); Xref=ChEBI:CHEBI:29103;
CC Evidence={ECO:0000250|UniProtKB:P0A817};
CC Note=Binds 1 potassium ion per subunit. The potassium ion interacts
CC primarily with the substrate. {ECO:0000250|UniProtKB:P31153};
CC -!- PATHWAY: Amino-acid biosynthesis; S-adenosyl-L-methionine biosynthesis;
CC S-adenosyl-L-methionine from L-methionine: step 1/1.
CC {ECO:0000250|UniProtKB:P31153}.
CC -!- SUBUNIT: Heterotrimer; composed of a catalytic MAT2A homodimer that
CC binds one regulatory MAT2B chain. Heterohexamer; composed of a central,
CC catalytic MAT2A homotetramer flanked on either side by a regulatory
CC MAT2B chain. {ECO:0000250|UniProtKB:P31153}.
CC -!- MISCELLANEOUS: Protein expression is regulated by post-transcriptional
CC regulation: in presence of S-adenosyl-L-methionine, METTL16 binds and
CC methylates the first hairpin of the 3'-UTR region of MAT2A mRNA,
CC preventing recognition of their 3'-splice site by U2AF1/U2AF35, thereby
CC inhibiting splicing and protein production of S-adenosylmethionine
CC synthase. In S-adenosyl-L-methionine-limiting conditions, METTL16 binds
CC the 3'-UTR region of MAT2A mRNA without methylating it due to the lack
CC of a methyl donor, preventing N6-methylation and promoting expression
CC of MAT2A. {ECO:0000250|UniProtKB:P31153}.
CC -!- SIMILARITY: Belongs to the AdoMet synthase family. {ECO:0000305}.
CC -!- CAUTION: According to a report, N6-methylation of MAT2A affects MAT2A
CC mRNA stability instead of preventing splicing (PubMed:29262316).
CC However, it was later shown that N6-methylation of MAT2A transcripts
CC prevents recognition of their 3'-splice site by U2AF1/U2AF35, thereby
CC inhibiting splicing and protein production (By similarity).
CC {ECO:0000250|UniProtKB:P31153, ECO:0000269|PubMed:29262316}.
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DR EMBL; AB070266; BAD06937.1; -; mRNA.
DR EMBL; AK166671; BAE38932.1; -; mRNA.
DR EMBL; AK168155; BAE40120.1; -; mRNA.
DR CCDS; CCDS39515.1; -.
DR RefSeq; NP_663544.1; NM_145569.4.
DR AlphaFoldDB; Q3THS6; -.
DR SMR; Q3THS6; -.
DR BioGRID; 231217; 17.
DR DIP; DIP-59526N; -.
DR IntAct; Q3THS6; 2.
DR STRING; 10090.ENSMUSP00000087118; -.
DR iPTMnet; Q3THS6; -.
DR PhosphoSitePlus; Q3THS6; -.
DR SwissPalm; Q3THS6; -.
DR EPD; Q3THS6; -.
DR jPOST; Q3THS6; -.
DR PaxDb; Q3THS6; -.
DR PeptideAtlas; Q3THS6; -.
DR PRIDE; Q3THS6; -.
DR ProteomicsDB; 295726; -.
DR Antibodypedia; 31867; 373 antibodies from 31 providers.
DR DNASU; 232087; -.
DR Ensembl; ENSMUST00000059472; ENSMUSP00000087118; ENSMUSG00000053907.
DR GeneID; 232087; -.
DR KEGG; mmu:232087; -.
DR UCSC; uc009cip.1; mouse.
DR CTD; 4144; -.
DR MGI; MGI:2443731; Mat2a.
DR VEuPathDB; HostDB:ENSMUSG00000053907; -.
DR eggNOG; KOG1506; Eukaryota.
DR GeneTree; ENSGT00950000183185; -.
DR HOGENOM; CLU_041802_0_1_1; -.
DR InParanoid; Q3THS6; -.
DR OMA; MPYLRPD; -.
DR OrthoDB; 685006at2759; -.
DR PhylomeDB; Q3THS6; -.
DR TreeFam; TF300511; -.
DR Reactome; R-MMU-156581; Methylation.
DR UniPathway; UPA00315; UER00080.
DR BioGRID-ORCS; 232087; 25 hits in 74 CRISPR screens.
DR ChiTaRS; Mat2a; mouse.
DR PRO; PR:Q3THS6; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; Q3THS6; protein.
DR Bgee; ENSMUSG00000053907; Expressed in embryonic post-anal tail and 64 other tissues.
DR ExpressionAtlas; Q3THS6; baseline and differential.
DR Genevisible; Q3THS6; MM.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0048269; C:methionine adenosyltransferase complex; ISS:UniProtKB.
DR GO; GO:0016597; F:amino acid binding; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004478; F:methionine adenosyltransferase activity; IDA:MGI.
DR GO; GO:1990830; P:cellular response to leukemia inhibitory factor; IEP:MGI.
DR GO; GO:0007623; P:circadian rhythm; ISO:MGI.
DR GO; GO:0006730; P:one-carbon metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0051291; P:protein heterooligomerization; ISS:UniProtKB.
DR GO; GO:0034214; P:protein hexamerization; ISS:UniProtKB.
DR GO; GO:0051591; P:response to cAMP; ISO:MGI.
DR GO; GO:0009725; P:response to hormone; ISO:MGI.
DR GO; GO:0009410; P:response to xenobiotic stimulus; ISO:MGI.
DR GO; GO:0006556; P:S-adenosylmethionine biosynthetic process; IDA:MGI.
DR HAMAP; MF_00086; S_AdoMet_synth1; 1.
DR InterPro; IPR022631; ADOMET_SYNTHASE_CS.
DR InterPro; IPR022630; S-AdoMet_synt_C.
DR InterPro; IPR022629; S-AdoMet_synt_central.
DR InterPro; IPR022628; S-AdoMet_synt_N.
DR InterPro; IPR002133; S-AdoMet_synthetase.
DR InterPro; IPR022636; S-AdoMet_synthetase_sfam.
DR PANTHER; PTHR11964; PTHR11964; 1.
DR Pfam; PF02773; S-AdoMet_synt_C; 1.
DR Pfam; PF02772; S-AdoMet_synt_M; 1.
DR Pfam; PF00438; S-AdoMet_synt_N; 1.
DR PIRSF; PIRSF000497; MAT; 1.
DR SUPFAM; SSF55973; SSF55973; 3.
DR TIGRFAMs; TIGR01034; metK; 1.
DR PROSITE; PS00376; ADOMET_SYNTHASE_1; 1.
DR PROSITE; PS00377; ADOMET_SYNTHASE_2; 1.
PE 1: Evidence at protein level;
KW Acetylation; ATP-binding; Isopeptide bond; Magnesium; Metal-binding;
KW Nucleotide-binding; One-carbon metabolism; Phosphoprotein; Potassium;
KW Reference proteome; Transferase; Ubl conjugation.
FT CHAIN 1..395
FT /note="S-adenosylmethionine synthase isoform type-2"
FT /id="PRO_0000174437"
FT REGION 113..125
FT /note="Flexible loop"
FT /evidence="ECO:0000250|UniProtKB:P0A817"
FT BINDING 29
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:P31153"
FT BINDING 31
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P31153"
FT BINDING 57
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /evidence="ECO:0000250|UniProtKB:P0A817"
FT BINDING 70
FT /ligand="L-methionine"
FT /ligand_id="ChEBI:CHEBI:57844"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:P31153"
FT BINDING 113
FT /ligand="L-methionine"
FT /ligand_id="ChEBI:CHEBI:57844"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:P31153"
FT BINDING 179..181
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:P31153"
FT BINDING 247..250
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:P31153"
FT BINDING 258
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:P31153"
FT BINDING 258
FT /ligand="L-methionine"
FT /ligand_id="ChEBI:CHEBI:57844"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /evidence="ECO:0000250|UniProtKB:P31153"
FT BINDING 264..265
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:P31153"
FT BINDING 281
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /evidence="ECO:0000250|UniProtKB:P31153"
FT BINDING 285
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /evidence="ECO:0000250|UniProtKB:P31153"
FT BINDING 289
FT /ligand="L-methionine"
FT /ligand_id="ChEBI:CHEBI:57844"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:P0A817"
FT BINDING 291
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="ligand shared between two neighboring
FT subunits"
FT /evidence="ECO:0000250|UniProtKB:P31153"
FT MOD_RES 81
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P31153"
FT MOD_RES 114
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P31153"
FT MOD_RES 384
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P31153"
FT CROSSLNK 228
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P31153"
FT CROSSLNK 234
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P31153"
FT CONFLICT 24
FT /note="S -> T (in Ref. 2; BAE40120)"
FT /evidence="ECO:0000305"
FT CONFLICT 128
FT /note="E -> G (in Ref. 1; BAD06937)"
FT /evidence="ECO:0000305"
FT CONFLICT 283
FT /note="S -> L (in Ref. 2; BAE38932)"
FT /evidence="ECO:0000305"
FT CONFLICT 302
FT /note="A -> S (in Ref. 2; BAE40120)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 395 AA; 43689 MW; BB977989B75CB8F9 CRC64;
MNGQLNGFHE AFIEEGTFLF TSESVGEGHP DKICDQISDA VLDAHLQQDP DAKVACETVA
KTGMILLAGE ITSRAAIDYQ KVVREAIKHI GYDDSSKGFD YKTCNVLVAL EQQSPDIAQG
VHLDRNEEDI GAGDQGLMFG YATDETEECM PLTIVLAHKL NAKLAELRRN GTLPWLRPDS
KTQVTVQYMQ DRGAVLPIRV HTIVISVQHD EEVCLDEMRD ALKEKVIKAV VPAKYLDEDT
IYHLQPSGRF VIGGPQGDAG LTGRKIIVDT YGGWGAHGGG AFSGKDYTKV DRSAAYAARW
VAKSLVKGGL CRRVLVQVSY AIGVSHPLSI SIFHYGTSQK SERELLEIVK KNFDLRPGVI
VRDLDLKKPI YQRTAAYGHF GRDSFPWEVP KKLKY
